The gelation of deoxyhemoglobin S is believed to cause the sickling of SS erythrocytes. The solubility assay for characterizing a deoxyhemoglobin S gel was used to search for potential antisickling agents. We found that although several peptides from the hemoglobin sequence enhanced gelation, the beta 82-91 peptide could inhibit gelation of deoxyhemoglobin S to the same extent as phenylalanine and the beta 84-85 (Thr-Phe) peptide. To study intracellular gelation, we developed an assay using 13C double resonance techniques. Data on samples of deoxyhemoglobin S gels obtained using 13C NMR were correlated with data obtained using the sedimentation technique on the same samples. A correction to the deoxyhemoglobin S solubility obtained from sedimentation was necessary due to concentration gradients introduced during ultracentrifugation. Having thus found agreement between the two techniques, studies of intracellular-gelation as a function of oxygen pressure on SS erythrocytes was begun.